The second-meal phenomenon is associated with enhanced muscle glycogen storage in humans.

The rise in blood glucose after lunch is less if breakfast has been eaten. The metabolic basis of this second-meal phenomenon remains uncertain. We hypothesized that storage of ingested glucose as glycogen could be responsible during the post-meal suppression of plasma NEFAs (non-esterified fatty acids; 'free' fatty acids). In the present study we determined the metabolic basis of the second-meal phenomenon. Healthy subjects were studied on two separate days, with breakfast and without breakfast in a random order. We studied metabolic changes after a standardized test lunch labelled with 3 g of 13C-labelled (99%) glucose. Changes in post-prandial muscle glycogen storage were measured using 13C magnetic resonance spectroscopy. The rise in plasma glucose after lunch was significantly less if breakfast had been taken (0.9+/-0.3 compared with 3.2+/-0.3 mmol/l, with and without breakfast respectively; P<0.001), despite comparable insulin responses. Pre-lunch NEFAs were suppressed after breakfast (0.13+/-0.03 compared with 0.51+/-0.04 mmol/l) and levels correlated positively with the maximum glucose rise after lunch (r=0.62, P=0.001). The increase in muscle glycogen signal was greater 5 h after lunch on the breakfast day (103+/-21 compared with 48+/-12 units; P<0.007) and correlated negatively with plasma NEFA concentrations before lunch (r=-0.48, P<0.05). The second-meal effect is associated with priming of muscle glycogen synthesis consequent upon sustained suppression of plasma NEFA concentrations.